Process for the synthesis of 3-methyl-pyridine

ABSTRACT

The present invention discloses a process for the synthesis of 3-methyl-pyridine from formaldehyde, paracetaldehyde, ammonia and acetic acid, whereby said compounds are reacted and said process comprises the following parameters:
         a) a reaction temperature of 260-300° C.;   b) a molar ratio of formaldehyde and paracetaldehyde of 0.7-1-4 Mol/Mol:   c) an ammonia concentration of 10-20 weight-%   d) an acetic acid concentration of 4-20 weight-%   e) a paracetaldehyde concentration of 0.4-1.6 Mol/kg   f) a retention time of 10-30 minutes in case of a continuous reaction and 10-90 minutes in case of a discontinuous reaction; and   g) a reaction pressure of 30-130 bar

The present invention concerns a process for the production of3-methyl-pyridine (3-picoline) from formaldehyde, paracetaldehyde,ammonia and acetic acid.

3-picoline is a colourless, flammable liquid which is used as a solvent,for the production of medicaments and insecticides as well as for thesynthesis of nicotinic acid and nicotine amide.

Several synthetic routes for the production of 3-picoline are known inthe art, which are generally based on an addition/cyclization reactionof aldehyde/keten mixtures with an ammonia compound. Said reactions canrun in the gas phase or in the liquid phase as well as using a catalyst.

The process according to the present invention is based on thepublication of Grayson, J. and Dinkel, R., “An improved Liquid-PhaseSynthesis of Simply Alkylpyridines”, Helvetica Chimica Acta, Vol. 67(1984), p. 2100-2110.

The authors of this publication describe in table 2, p. 2108 inter aliathe synthesis of 3-picoline from acetaldehyde an formaldehyde, wherebydifferent ammonia sources are compared with regard to 3-picolin yield aswell as to the presence of diverse, unwanted side products.

In particular, it is shown that the use of ammonia acetate results in ayield of 44%, whereby 3-ethylpyridin as the main side product is presentin an amount of 18%.

Thus, the technical problem to be solved is to improve the process ofGrayson and Dinkel with regard to 3-picolin yield, reduction of3-ethylpyridine amount as main side product as well as an increase inthe space/time yield.

Said problem is surprisingly solved by the process according to thepresent invention for the synthesis of 3-methyl-pyridine fromformaldehyde, paracetaldehyde, ammonia and acetic acid, whereby saidcompounds are reacted and said process comprises the followingparameters:

-   -   a) a reaction temperature of 260-300° C.;    -   b) a molar ratio of formaldehyde and paracetaldehyde of 0.7-1-4        Mol/Mol:    -   c) an ammonia concentration of 10-20 weight-%    -   d) an acetic acid concentration of 4-20 weight-%    -   e) a paracetaldehyde concentration of 0.4-1.6 Mol/kg    -   f) a retention time of 10-30 minutes in case of a continuous        reaction and 10-90 minutes in case of a discontinuous reaction;        and    -   g) a reaction pressure of 30-130 bar

It may be preferred that the reaction takes place in a reactor. Morepreferably, said reactor is a system with a high efficiency of mixinglike stirring devices as well as continuous flow-through stirrer vesselsand discontinuous stirrer vessels. Most preferably, said reactor is aloop-reactor or jet-loop-reactor.

Loop- and jet-loop-reactors according to the invention are characterizedby the fact that the respective reactants are brought to reaction withthe catalyst-solution in a continuous manner. One major advantage ofjet-loop-reactors compared to stirrer vessels for the production of3-picoline is the more intensive and faster mixing of fluids whenoperating under a high circulation stream, resulting in an increasedpassage of heat and material. Preferably, the process according to theinvention is operated in a loop reactor with stream zones. Anotheradvantage of stream-powered loop reactors is a finer dispersion of theadded phases and thus a bigger specific interphase.

Furthermore, it may be preferred that side products are removed in theprocess of re-cycling the catalyst. Generally, all technical means knownin the art can be employed, like e.g. extraction and rectification.Especially preferred is distillation.

The process according to the invention contemplates the addition ofammonia and formaldehyde both in molecular form as well as in form oftheir addition product hexamethylene-tetratimne (Urotropine).

The process according to the invention is distinguished from the priorart according to Dinkel et al. inter alia by combining a higherselectivity with regard to the formation of 3-methylpyridine with anincreased space/time yield. This results in a major technical advantage,since normally an increased space/time yield results in a decrease inselectivity.

The process according to the present invention is further explained bythe following, non-limiting example.

EXAMPLE 1

The reaction takes place continuously in a 100 Litre reactor with a veryhigh degree of mixing. Pumps are used to add the catalyst solution (amixture of water, ammonia and acetic acid) and the educts(paracetaldehyde and formalin).

261 kg/h of catalyst solution (75 weight-% water, 15 weight-% ammoniaand 10 weight-% acetic acid) are brought into the reactor viahigh-pressure pumps. Simultaneously, 13 kg/h paracetaldehyde and 26.8kg/h formalin solution (37.4 weight-%) are added continuously viahigh-pressure pumps. The reactor temperature is kept at 278° C. and thereactor pressure at 100 bar. A retention time of 20 minutes results in acrude solution containing 10.02 kg/h 3-picolin and 0.37 kg/h3-ethylpyridine. Under these condition, a 3-picolin yield of 64.6%(based on formaldehyde) and a 3-ethylpyridine yield of 3.5% (based onacetaldehyde) is achieved. All pyridine bases were analyzed via gaschromatography.

1). A process for the synthesis of 3-methyl-pyridine from formaldehyde,paracetaldehyde, ammonia and acetic acid, whereby said compounds arereacted and said process comprises the following parameters: a) areaction temperature of 260-300° C.; b) a molar ratio of formaldehydeand paracetaldehyde of 0.7-1-4 Mol/Mol: c) an ammonia concentration of10-20 weight-% d) an acetic acid concentration of 4-20 weight-% e) aparacetaldehyde concentration of 0.4-1.6 Mol/kg f) a retention time of10-30 minutes in case of a continuous reaction and 10-90 minutes in caseof a discontinuous reaction; and g) a reaction pressure of 30-130 bar)2). A process according to claim 1, whereby said process takes place ina reactor system with a high efficiency of mixing 3.) Process accordingto claim 2, whereby said reactor system is a continuous or discontinuousflow-through stirrer vessel.) 4). Process according to claim 2, wherebysaid reactor system is a loop-reactor.) 5). Process according to claim1, whereby side products are removed in the process of re-cycling thecatalyst.) 6). Process according to claim 5, whereby said side productsare removed via rectification or extraction.
 7. Process according toclaim 1, whereby the space/time yield of 3-methylpyridine is more than50 kg/m³*h, preferably more than 80 kg/m³*h and most preferably morethan 100 kg/m³*h.)
 8. Process according to claim 1, whereby the3-methylpyridine yield is at least 64% (based on formaldehyde) and the3-ethylpyridine yield is at most 4% (based on paracetaldehyd).